Entrectinib approval by EMA reinforces options for ROS1 and tumour agnostic NTRK targeted cancer therapies

On 28 May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the granting of a conditional marketing authorisation for entrectinib (Rozlytrek), for the treatment of patients whose solid tumours have a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion or for patients with ROS1 fusion-positive advanced non-small cell lung cancer (NSCLC).1 Based on the full indication, entrectinib represents a new therapeutic option for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours NTRK fusion-positive, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options. In addition, entrectinib is indicated as monotherapy for the treatment of adult patients with ROS1 fusion-positive, advanced NSCLC not previously treated with ROS1 inhibitors. The present CHMP recommendation is based on the analysis of combined results of four clinical studies, the pivotal phase II STARTRK-2, the ALKA-372–001 and the STARTRK-1 phase I trials, and the phase I/II STARTRK-NG paediatric study.2 Overall in these studies, the efficacy of entrectinib was observed in patients with NTRK fusion-positive locally advanced or metastatic tumours, with an objective response rate (ORR) of 63.5% and a median duration of response (DoR) of 12.9 months.2 The clinical benefit reported across several different NTRK fusion-positive tumour types is in our opinion a very compelling evidence and supports the tissue-agnostic indication approval for entrectinib. This approval would represent the second case, after larotrectinib, of an EMA granted approval based on a common driver molecular alteration across different tumour types rather than on tumour histology. In ROS1 fusion-positive advanced NSCLC patients enrolled in the trials, entrectinib achieved ORR in 73.4% of cases with …